Heart rate variability in perinatal risk populations: A systematic review and meta-analysis

ImportanceIndividuals exposed to perinatal risk factors are at increased risk for cardiovascular and neurodevelopmental disorders. Heart rate variability, an index of autonomic nervous system function, is widely used to assess long-term health risk in these populations, yet findings remain inconsistent. ObjectiveTo quantify heart rate variability differences between individuals with perinatal risk factors (including preterm birth, intrauterine growth restriction, and low birth weight) and healthy full-term controls, and to examine sources of heterogeneity. Data sourcesPubMed, EMBASE, Web of Science, Scopus, and APA PsycArticles were searched through April 2025, supplemented by ClinicalTrials.gov and reference screening. Study selection: Peer-reviewed studies reporting heart rate variability in perinatal risk populations versus healthy controls after hospital discharge. Of 7,781 screened articles, 27 met inclusion criteria. Data extraction and synthesisThis review followed PRISMA 2020 guidelines and was registered on PROSPERO (CRD42024527673). One reviewer extracted data using a standardized form, with verification by a second reviewer. A total of 176 effect sizes were extracted. Multilevel random-effects models accounted for dependency within studies. Main outcome(s) and measure(s)The primary outcome was heart rate variability difference between groups, expressed as Cohens d. ResultsAcross 27 studies (1,890 participants) and 176 effect sizes, the overall effect was modest and marginally significant (d = -0.24; 95% CI: -0.50 to 0.02; p = 0.07), with substantial heterogeneity (I{superscript 2} = 87.7%). Effect sizes differed significantly by perinatal condition (p < 0.001). Congenital heart disease (d = -1.07) and genetic syndromes (d = - 1.02) showed large heart rate variability reductions, while growth-related conditions showed moderate effects (d = -0.44). Heart rate variability differences attenuated with age ({beta} = +0.027 per year; p = 0.04), with strongest effects in early development (d = -0.85) and apparent normalization during adolescence. Conclusions and relevanceAutonomic consequences of perinatal adversity are condition-specific and developmentally dynamic. Structural and genetic conditions show pronounced deficits, while other conditions show substantial developmental heterogeneity. These findings underscore the importance of age- and condition-specific assessment and longitudinal follow-up. Key PointsO_ST_ABSQuestionC_ST_ABSDo individuals with perinatal risk factors show altered heart rate variability (HRV) compared to healthy controls, and what factors explain between-study heterogeneity? FindingsIn this meta-analysis of 27 studies, perinatal risk groups showed modestly reduced HRV compared to controls, with effects varying significantly by condition. Congenital heart disease and genetic syndromes showed large HRV reductions. Growth-related conditions showed moderate reductions. HRV differences were largest in early development and attenuated significantly with age. MeaningAutonomic consequences of perinatal adversity are condition-specific and developmentally dynamic, warranting age- and condition-specific clinical assessment.